Replies to post #316079 on NorthWest Biotherapeutics Inc (NWBO)

[Chiugray]

Makes a great deal of sense.

It would be incredibly risky to unblind if the SAP has not been bought in by the FDA. If the SAP needs to be adjusted then NWBO can be easily accused of post hoc data mining...
I personally believe NWBO waited for the buy in of SAP/endpoints either in Europe and or with the FDA which could have contributed to the recent delay.

[exwannabe]

The FDA would not deny the endpoint change. They can only do so if the change effects patient safety.

The FDA would provide a non-binding opinion that the change may not be suitable for use in registration trial. As vrbru notes, that will be a wishy-washy language.

The modified SAP also might never have been officially submitted. They could have asked the FDA for an opinion and decided not to submit. They have never said they submitted, only a forward looking statement that they planned to.

Now, why do you think they never said they actually have submitted the SAP and the FDA accepted it?

Had they done so, that would not be a forward looking statement but a statement of fact. And a material lack of completeness wrt an FDA negative opinion could be a problem.

BTW, it has happened in the past that a company played the same game. Vical. Very similar story. Trial running late because of slow OS events. Trial not unblinded at PFS as they waited for OS. Company tried to change endpoints to make OS primary.

That time though they had a SPA so the FDA could and did reject it. I doubt the investors who lost almost all feel happy to know the lack of disclosure was arguable a violation of law.

[antihama]

I did not read the article but what you state in point 1 is contrary to my understanding of the process. The FDA does not approve protocol changes. You need to notify them of the change only. You hope to have them on board w these changes but you are free to put those changes into the protocol assuming patient safety is not affected (it does need IRB approval). You can request a meeting w them to get their comments and meeting minutes but they would not have denied the SAP changes. So how can it be material? Again, I can see a scenario where the EU was on board w the changes while the US was holding out and they said heck, let’s issue the revised SAP (only one SAP per protocol) and hope the US comes on board later on. What happens if they never do? Let’s say, worst case, it plays out to one of Ex’s scenario’s where NWBO was never truly blinded, and therefore shouldn’t have revised the SAP. I can see the FDA having an Advisory Committee meeting to vote on it and hopefully, the KOLs on the committee saying to the Agency “What are you stupid, of course this drug if efficacious and gives DCVAX-L a positive vote, and the Agency goes along w the vote to approve it but that’s worst case. I see it playing out like my edit scenario

EDIT: OR they finally, finally had buy-in from the FDA but still didn't receive the official meeting minutes (to be issued by the FDA within 30 days). NWBO said OK that's close enough! Lets get the EU protocol updated but they still can't PR till they get the official minutes from the FDA. I like this scenario!

Until we get a PR of these major endpoint changes that the way I see it. Here’s an example of a major endpoint change PR
Halozyme Announces Change In Primary Endpoint For HALO-301 To Overall Survival

11/26/2018
-FDA Agrees to Company Request to Change Primary Endpoint to Overall Survival-
-Previously Planned Interim Analysis Will Not Be Conducted-
-Management to Host Webcast / Conference Call Today at 5 p.m. ET / 2 p.m. PT-

https://www.halozyme.com/investors/news-releases/news-release-details/2018/Halozyme-Announces-Change-In-Primary-Endpoint-For-HALO-301-To-Overall-Survival/default.aspx